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Prevalence and clinical outcomes of germline variants among patients with myeloid neoplasms
  1. Sunisa Kongkiatkamon1,2,
  2. Pimjai Niparuck3,
  3. Thanawat Rattanathammethee4,
  4. Sirorat Kobbuaklee1,2,
  5. Amornchai Suksusut1,2,
  6. Kitsada Wudhikarn1,2,
  7. Chupong Ittiwut5,6,
  8. Wanna Chetruengchai5,6,
  9. Suporn Chuncharunee3,
  10. Udomsak Bunworasate1,2,
  11. Kanya Suphapeetiporn5,6,
  12. Ponlapat Rojnuckarin1,2,
  13. Chantana Polprasert1,2
  1. 1Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
  2. 2Center of Excellence in Translational Hematology, Chulalongkorn University, Bangkok, Thailand
  3. 3Department of Medicine, Faculty of Medicine, Mahidol University Ramathibodi Hospital, Bangkok, Thailand
  4. 4Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
  5. 5Center of Excellence for Medical Genomics, Medical Genomics Cluster, Department of Pediatrics,Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
  6. 6Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, Thailand
  1. Correspondence to Dr Chantana Polprasert, Department of Medicine, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand; jeedchantana{at}


Aims Myeloid neoplasms (MNs) with germline predisposition have been recognised as a distinct entity. Emerging evidence suggests that sporadic myelodysplastic syndromes may also harbour undetected germline predispositions. We investigated germline alterations in a cohort of 122 adult Thai MNs.

Methods MN patients were recruited and tested for germline variants using deep targeted next-generation sequencing. The germline variant was filtered using American College of Medical Genetics classifications and then evaluated for the association with clinical characteristics and outcomes.

Results Our findings revealed pathogenic/likely pathogenic germline alterations in 12 (10%) of the patients. These germline lesions were commonly found in the DNA damage response pathway (n=6, 50%). We also identified novel deleterious FANCAA1219GfsTer59 variants in two patients diagnosed with secondary acute myeloid leukaemia (sAML) from aplastic anaemia and AML with myelodysplasia related. Among sAML, individuals with germline mutations had inferior overall survival compared with those with wild-type alleles (2 months vs 12 months) with HR 4.7 (95% CI 1.0 to 20), p=0.037. Therefore, the presence of pathogenic or likely pathogenic mutations may be linked to inferior survival outcomes.

Conclusions Our study highlighted that the prevalence of germline predisposition in Southeast Asian populations is comparable to that in Caucasians. This underscores the importance of germline genetic testing within the Asian population.

  • Leukemia, Myeloid
  • Genes, Neoplasm
  • Hematologic Diseases

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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  • Handling editor Vikram Deshpande.

  • Contributors SKongkiatkamon designed the research study, acquired data, analysed data and wrote the draft manuscript. PN collected data and provided and cared for study patients. TRattanathammethee collected data provided and cared for study patients and edited the manuscript. KW provided and cared for study patients and served as scientific advisors. SKobbuaklee performed targeted sequencing. AS performed targeted sequencing. CI analysed sequencing data. WC analysed sequencing data. SC collected data and provided and cared for study patients. UB collected data and provided and cared for study patients. KS served as scientific advisors. PR provided and cared for study patients, served as scientific advisors and edited the manuscript. CP conceived and conceptualised the research study,collected data and had a full resposibility for the overall content in this mauscript. All authors read and edited the manuscript.

  • Funding This work was supported by grants from the Fundamental fund (The Thai Red Cross education and research committee) (SKongkiatkamon), Ratchadapiseksompotch Fund, Graduate Affairs, Faculty of Medicine, Chulalongkorn University, Grant number GA65/77 (SKongkiatkamon), Thailand Research Fund (grant number RDG6050109, RGU6280006; CP) the Center of Excellence in Translational Hematology (CP), the Thai Society of Hematology (CP) and Anandamahidol Foundation (CP).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.